title: Force-activated reactivity switch in a bimolecular chemical reaction.
abstract: The effect of mechanical force on the free-energy surface that governs a chemical reaction is largely unknown. The combination of protein engineering with single-molecule force-clamp spectroscopy allows us to study the influence of mechanical force on the rate at which a protein disulfide bond is reduced by nucleophiles in a bimolecular substitution reaction (S(N)2). We found that cleavage of a protein disulfide bond by hydroxide anions exhibits an abrupt reactivity 'switch' at ∼500 pN, after which the accelerating effect of force on the rate of an S(N)2 chemical reaction greatly diminishes. We propose that an abrupt force-induced conformational change of the protein disulfide bond shifts its ground state, drastically changing its reactivity in S(N)2 chemical reactions. Our experiments directly demonstrate the action of a force-activated switch in the chemical reactivity of a single molecule.
authors.affiliation: Department of Biological Sciences, Columbia University, New York, New York 10027, USA. sergi@biology.columbia.edu
authors.forename: Sergi
authors.initials: S
authors.lastname: Garcia-Manyes
authors.forename: Jian
authors.initials: J
authors.lastname: Liang
authors.forename: Robert
authors.initials: R
authors.lastname: Szoszkiewicz
authors.forename: Tzu-Ling
authors.initials: TL
authors.lastname: Kuo
authors.forename: Julio M
authors.initials: JM
authors.lastname: Fernández
mesh_terms: D019943:Amino Acid Substitution; D064211:Connectin; D004220:Disulfides / Q000737:chemistry; D006878:Hydroxides / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D009124:Muscle Proteins / Q000737:chemistry; D015202:Protein Engineering; D011494:Protein Kinases / Q000737:chemistry; D011506:Proteins / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D064211:Connectin; D004220:Disulfides; D006878:Hydroxides; D046911:Macromolecular Substances; D009124:Muscle Proteins; D011506:Proteins; C031356:hydroxide ion; D011494:Protein Kinases